ERBB2 promoter binding protein in neoplastic disease

Abstract

The present invention provides a purified and isolated DNA-binding protein, HPBF, which specifically binds to the promoter region of the Her-2/neu (ERBB2/c-erbB-2) gene sequence, the presence of which provides an early indication of transition to a cancerous state has been found. The present invention also provides bioassays for screening substances for the ability to inhibit HPBF activity, the ability to inhibit the mitogenic activity of HPBF and the ability to inhibit HPBF production. The present invention further provides methods of inhibiting the biological activity mediated by HPBF comprising preventing the HPBF from binding to the promoter region of the ERBB2 gene sequence.

What is claimed is: 
     
       1. A method of detecting the presence of a cancer correlated with the presence of Her-2/neu promoter binding factor, in a subject comprising determining the presence of a detectable amount of Her-2/neu promoter binding factor in a biological sample from the subject, the presence of a detectable amount of Her-2/neu promoter binding factor relative to the absence of Her-2/neu promoter binding factor in a normal control indicating the presence of a cancer correlated with the presence of Her-2/neu promoter binding factor. 
     
     
       2. A method of determining the prognosis of a subject having a cancer correlated with the presence of Her-2/neu promoter binding factor, comprising determining the presence of a detectable amount of Her-2/neu promoter binding factor in a biological sample from a subject, the presence of a detectable amount of Her-2/neu promoter binding factor relative to the absence of Her-2/neu promoter binding factor in a normal control indicating a decreased chance of long term survival. 
     
     
       3. The method of claim 1, wherein the presence of a detectable amount of Her-2/neu promoter binding factor is determined by a) contacting the biological sample with a nucleic acid to which the HPBF binds under conditions such that an HPBF/nucleic acid complex can be formed; and   b) detecting the formation of the HPBF/nucleic acid complex, the formation of the complex indicating the presence of HPBF in the biological sample.   
     
     
       4. The method of claim 3, wherein the nucleic acid is the nucleic acid set forth in SEQ ID NO:3. 
     
     
       5. The method of claim 1, wherein the presence of a detectable amount of Her-2/neu promoter factor is determined by a) contacting the biological sample with an antibody which specifically binds HPBF under conditions such that an HPBF/antibody complex can be formed; and   b) detecting the formation of the HPBF/antibody complex, the formation of the complex indicating the presence of HPBF in the biological sample.   
     
     
       6. The method of claim 5, wherein the antibody is conjugated to a detectable moiety. 
     
     
       7. The method of claim 6, wherein the antibody is bound to a solid support. 
     
     
       8. The method of claim 2, wherein the presence of a detectable amount of Her-2/neu promoter binding factor is determined by a) contacting the biological sample with a nucleic acid to which the Her-2/neu promoter binding factor binds under conditions such that an Her-2/neu promoter binding factor/nucleic acid complex can be formed; and   b) detecting the formation of the Her-2/neu promoter binding factor/nucleic acid complex, the formation of the complex indicating the presence of Her-2/neu promoter binding factor in the biological sample.   
     
     
       9. The method of claim 8, wherein the nucleic acid is the nucleic acid set forth in SEQ ID NO:3. 
     
     
       10. The method of claim 2, wherein the presence of a detectable amount of Her-2/neu promoter binding factor is determined by a) contacting the biological sample with an antibody which specifically binds Her-2/neu promoter binding factor under conditions such that an Her-2/neu promoter binding factor/antibody complex can be formed; and   b) detecting the formation of the Her-2/neu promoter binding factor/antibody complex, the formation of the complex indicating the presence of Her-2/neu promoter binding factor in the biological sample.   
     
     
       11. The method of claim 10, wherein the antibody is conjugated to a detectable moiety. 
     
     
       12. The method of claim 10, wherein the antibody is bound to a solid support. 
     
     
       13. The method of claim 1, wherein the cancer is breast cancer. 
     
     
       14. The method of claim 2, wherein the cancer is breast cancer.